SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is ...currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4+ and CD8+ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects.
•SARS-CoV-2 vertical mother-to-child transmission was confirmed to be a rare event.•The immunological response among infected mothers was good.•An effective transfer of anti-SARS-CoV-2 antibodies to ...the newborn was detected.•Vaccination during pregnancy should also be endorsed to protect infants aged <6 months old.
To assay the presence of the SARS-CoV-2 genome in vaginal, rectal, and placental swabs among pregnant women and in newborn nasopharyngeal swabs and to investigate the immunological response and maternal antibody transfer through the umbilical cord blood and milk of unvaccinated mothers.
Vaginal, rectal, and placental specimens, maternal and neonatal serum, and milk were collected from a wide cohort of pregnant Italian women with confirmed SARS-CoV-2 infection admitted to the hospital between February 25, 2020 and June 30, 2021. Samples were tested in selected reference laboratories according to a shared interlaboratory protocol.
Among 1086 enrolled women, the SARS-CoV-2 positive rate detected in all specimens ranged from 0.7% to 8.4%. Respectively, 45.2% of maternal sera collected during pregnancy and 39.7% of those collected at birth tested positive for immunoglobulin G, whereas 50.5% tested positive among neonates. Nasopharyngeal swabs were positive in 0.8% of the newborns, and immunoglobulin G was detected in 3.0% of the milk samples. The highest immunological response was recorded within 30 days during pregnancy and within 60 days of birth and in the neonatal population.
Vertical transmission should be considered a rare event; although, a good maternal immunological response and antibodies transfer throughout the umbilical cord blood was detected.
Background:
In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are ...subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures.
Objectives:
In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs.
Study design:
We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples “Federico II” between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48.
Results:
One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (
p
= 0.086), 0.15 (
p
= 0.124), and 0.034 (
p
= 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (
p
< 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites.
Conclusions:
Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.
The low response to vaccines is a well-known problem in cirrhosis. We evaluated the safety and immunogenicity of booster doses in patients with chronic liver disease (CLD), comparing the humoral ...response in cirrhotic vs. non-cirrhotic patients, and the impact of different factors on immune response. From September 2021 to April 2022, outpatients with CLD who completed the primary vaccination course and the booster dose against SARS-CoV-2 were enrolled. Blood samples were collected after second and third doses for detecting anti-spike protein IgG. We enrolled 340 patients; among them, 91 subjects were cirrhotic. After primary vaccination course, 60 (17.6%) patients did not develop a positive antibody titer, without significant differences between cirrhotic and non-cirrhotic patients (
= 0.076); most of them (88.3%) developed it after booster dose. At multivariable analysis, factors associated with higher humoral response after booster dose were only porto-sinusoidal vascular disorder (
= 0.007) as an etiology of CLD and the use of the mRNA-1273 vaccine (
= 0.001). In conclusion, in patients with CLD, a booster dose against SARS-CoV-2 induces an excellent immunogenicity and leads to an adequate antibody response. Cirrhosis is not associated with a worse humoral response, compared to patients with non-cirrhotic CLD.
Systemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including ...procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients.
Ninety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support.
Serum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 PIIINP: 7.2 (5.4-9.5) vs. 7.1 (4.5-9.9),
= 0.782; TIMP-1: 298.1 (20.5-460) vs. 222.2 (28.5-452.8),
= 0.01; HA: 117.1 (55.4-193.7) vs. 75.1 (36.9-141.8),
= 0.258. TIMP-1 showed moderate correlation with CRP (r = 0.312,
= 0.003) and with LDH (r = 0.263,
= 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 15.8 (9-44.5) vs. 9.3 (3.4-33.8),
= 0.039 and 373 (282-465) vs. 289 (218-383),
= 0.013, respectively.
In patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.
Heterophilic antibodies can interfere with laboratory tests causing erroneous results. We report the case of a 55-year-old man with Mantle cell myeloma treated with Rituximab that caused false ...positive results of HIV serologic test. The cause of this interference was investigated, and very high levels (741 ng/ml) of human anti-mouse antibodies (HAMA) were demonstrated. Polyethylene glycol (PEG) precipitation of intact immunoglobulins was used to cross-check the antibody-related interference. The PEG treatment negativized the HIV test outcome, confirming that the cause of the false positive serologic HIV result was due to interference caused by HAMA. In conclusion, we suggest to cautiously interpreting laboratory findings in patients treated with Rituximab because of the possibility that HAMA may cause interference in serological assays.
Background and Aims
The prevalence of HDV infection in HBsAg carriers is about 9.9% in Italy. However, the real prevalence is underestimated because the anti‐HDV test is not performed routinely in ...all HBsAg carriers. The aim of this study was to compare the prevalence and the absolute number of HDV infection identified in HBsAg‐positive subjects tested at University Hospital Federico II before and after the introduction of anti‐HDV reflex testing.
Methods
From January to December 2022, reflex test for the detection of total HDV antibodies was performed in all HBsAg‐positive subjects tested at University Hospital Federico II. The control group consisted of all the HBsAg‐positive subjects tested at the same laboratory in 2019, before the implementation of anti‐HDV reflex testing. Sera were evaluated with ADVIA Centaur HBsAgII Qualitative, Liaison Murex HBsAg Quantitative and Liaison Murex Total Anti‐HDV Qualitative.
Results
Before reflex testing, anti‐HDV had been tested in 16.4% (84/512) of HBsAg‐positive subjects, while after its implementation, 100% (484/484) of HBsAg‐positive patients was tested for anti‐HDV. The anti‐HDV positive prevalence was lower than before the introduction of reflex test (10.7% vs. 16.6%) but the absolute number of anti‐HDV positive patients increased (14 vs. 52 subjects). HDV‐RNA was detectable in 26 (53%) of 49 tested subjects.
Conclusions
Our data showed that the implementation of anti‐HDV reflex testing increased the diagnoses of HDV infection. In this setting, due to the approval of specific anti‐HDV drugs, a reflex test for anti‐HDV should be implemented to early identify patients with HBV/HDV infection.
Since the beginning of the pandemic, SARS‐CoV‐2 has shown a great genomic variability, resulting in the continuous emergence of new variants that has made their global monitoring and study a ...priority. This work aimed to study the genomic heterogeneity, the temporal origin, the rate of viral evolution and the population dynamics of the main circulating variants (20E.EU1, Alpha and Delta) in Italy, in August 2020–January 2022 period. For phylogenetic analyses, three datasets were set up, each for a different main lineage/variant circulating in Italy in that time including other Italian and International sequences of the same lineage/variant, available in GISAID sampled in the same times. The international dataset showed 26 (23% Italians, 23% singleton, 54% mixed), 40 (60% mixed, 37.5% Italians, 1 singleton) and 42 (85.7% mixed, 9.5% singleton, 4.8% Italians) clusters with at least one Italian sequence, in 20E.EU1 clade, Alpha and Delta variants, respectively. The estimation of tMRCAs in the Italian clusters (including >70% of genomes from Italy) showed that in all the lineage/variant, the earliest clusters were the largest in size and the most persistent in time and frequently mixed. Isolates from the major Italian Islands tended to segregate in clusters more frequently than those from other part of Italy. The study of infection dynamics showed a positive correlation between the trend in the effective number of infections estimated by BSP model and the Re curves estimated by birth‐death skyline plot. The present work highlighted different evolutionary dynamics of studied lineages with high concordance between epidemiological parameters estimation and phylodynamic trends suggesting that the mechanism of replacement of the SARS‐CoV‐2 variants must be related to a complex of factors involving the transmissibility, as well as the implementation of control measures, and the level of cross‐immunization within the population.
